Pioped 3 trial

Description: Alteplase for angiographic outcomes in pulmonary embolism. Hypothesis: 1 rt-PA in combination with heparin has potential for the treatment of acute pulmonary embolism. Primary Endpoints: Fragment-D dimers in vivo clot lysis indicator , total pulmonary resistance. Secondary Endpoints: Occlusion grade , size grade 0. Interpretation: PIOPED rt-PA randomized trial: The observations in this study suggest that rt-PA has little effect in two hours on angiographic clot burden, but may produce some improvement in hemodynamics.

Negative CT angiogram and negative venous phase CT venogram in a patient with a low or intermediate clinical probability by the Wells criteria. After February 20, , the protocol was revised to permit a negative ultrasound of the legs if CT venography is not obtained. Low probability V-Q lung scan, low clinical probability by Wells criteria, and negative venous ultrasound. Some of these patients had a very low probability V-Q scan interpretation 26 , The study excludes patients from further investigation if a definitive diagnosis or exclusion of PE cannot be achieved.

All patients undergoing CT angiography will also undergo venous phase CT venography in combination. Therefore, after nearly 2 years of recruitment, some centers substituted venous ultrasound for CT venography. Untreated patients in whom PE was excluded by the composite reference test will be followed 3 months.

A positive clinical outcome may reverse a negative reference test. The composite criteria for the diagnosis or exclusion of PE eliminates the ethical problem of asking patients to volunteer for a conventional DSA, which carries some risk, although the risk is small This would give an unnecessarily narrow confidence interval for specificity at great financial cost, diminished feasibility, and burden on a large number of patients.

It would cause overloading of heavily scheduled magnetic resonance imaging systems and perhaps raise a question on the ethics of investigating so many normal subjects.

The Data and Coordinating Center will manage the computer-based random sampling system to achieve approximately equal numbers of patients positive and negative by the reference standard. The goal is to achieve an approximately equal number of subjects with and without PE. Investigators from each clinical center may serve as central readers of images from other centers. Central readers will not re-interpret venous compression ultrasounds. Central readers will not have clinical information, nor will they have the results of other imaging studies except chest roentgenograms for V-Q readers.

Adjudication for V-Q scans will be required if there is disagreement on the diagnostic probability high probability, intermediate probability, low probability or normal. Adjudicated readings will be performed blindly by a third reader without knowledge of the other two readings.

Each central reader will be certified as having participated in training prior to reading any images for the study. Reader variability will be compared in central readers on the basis of detailed per-vessel readings. Differences between central and local readers on whether PE is present or absent also will be determined. Potential differences between local and central interpretations of diagnostic images will not result in many lost cases.

Final interpretation would be based on the central reading except venous ultrasound. If the local reading is negative and the central reading is positive and if the patient is randomized for a Gd-MRA, all of the necessary data would be obtained.

An important design requirement for a study of diagnostic accuracy is that the study should include a wide spectrum of patients having the condition to be diagnosed 32 , Gadolinium enhanced Gd-MRA will be obtained within 72 hours of the definitive imaging study. At one center University of Michigan a 3. The protocol is otherwise analogous to that designed for the 1.

At all centers, parallel imaging will be used. Thus, a specialized multichannel channel phased array coil will be used for reception of the pulmonary MRA data. The body coil will be used for signal transmission. All scout imaging of both the chest and thighs will be obtained at the beginning of the examination with the table prescribed to move to the thigh station automatically.

A torso multichannel phased array coil will be used for the pulmonary Gd-MRA. Magnetic resonance venography of the thigh will be performed with the body coil. A single bolus of gadolinium-containing contrast material timed to the main pulmonary artery will be used for all imaging, with multiple measures data acquisitions obtained immediately and consecutively in the thighs to avoid missing the maximal venous opacification.

A gauge catheter will be placed in an antecubital vein and connected to a power injector by an intravenous tubing extension. The patient will be positioned supine within the bore of the magnet. Sagittal and transverse locators will be performed at the thorax, centered at the midline in the left-to-right direction and at the nipple line in the superior-to-inferior direction. A second coronal locator will be acquired mid thighs for graphical thigh MRV prescription.

In large or obese patients, phase wrap artifact can be a significant problem with parallel imaging. For studies in which phase wrap is likely to occur, parallel imaging will not be used. With obese patients the breath-hold length no more than 22 sec and field of view will be kept constant 40 cm and the matrix will be reduced, thus decreasing the in-plane resolution in the phase-encoding direction.

The coronal volume will be prescribed from the midline sagittal or transverse locator slice. The posterior aspect of the imaging volume will be placed in the thorax at or near the posterior border of the vertebral body at the level of the heart.

The position of the imaging volume will be set to ensure that the descending pulmonary arteries, segmental and proximal subsegmental branches are included in the imaging region. Imaging time breath hold will be approximately seconds. A partially occlusive intraluminal filling. Complete arterial occlusion with termination of the column of contrast material in a meniscus that outlines the trailing edge of the embolus Total examination time for Gd-MRA of the pulmonary arteries will be 20 minutes.

This includes scout scanning for position of the images and the test bolus. With newer 1. This permits an improved signal-to-noise ratio in the legs.

Some have used Gd-MRA to show pulmonary perfusion based on filling of small vessels This is analogous to the perfusion phase of a pulmonary angiogram, which has been shown to be useful, but nonspecific It is also analogous to a perfusion lung scan.

Most perfusion studies have been physiological investigations 38 - Those that have focused on detection of perfusion defects from PE have been preliminary and showed inconclusive results 36 , 41 , Newer time-resolved three-dimensional contrast enhanced MR angiography sequences, such as Time-Resolved Imaging of Contrast Kinetics TRICKS , that can provide both pulmonary angiography and perfusion in a single breath-hold sequence, have been developed 43 , In addition, they typically provide lower spatial resolution MRA images in comparison to non-time resolved methods.

Upon completion of the pulmonary MRA, MR venography of the thighs will be performed with the table prescribed to immediately move to the region of scout of the thighs performed at the beginning of the examination.

The same imaging sequence performed for pulmonary Gd-MR angiography will be performed in the thighs with minor modifications of the parameters. Delayed MR venography will be performed using a transmit and receive body coil and 3D gradient-recalled echo sequence.

Parallel imaging will not be used, as breath holding is not an issue. Six measurements will be performed in rapid succession prior to image construction in order to ensure that the bolus is not missed. Each measurement will take approximately 30 seconds. Imaging will be prescribed in the coronal plane to cover the thighs from the acetabulum to the tibial plateaus.

The posterior aspect of the imaging volume will be set at the sacrum and the anterior aspect set anterior to the pubic symphysis to encompass femoral to popliteal veins. Conclusion: Magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Magnetic resonance pulmonary angiography and magnetic resonance venography combined have a higher sensitivity than magnetic resonance pulmonary angiography alone in patients with technically adequate images, but it is more difficult to obtain technically adequate images with the 2 procedures.

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